Testicular Dysgenesis Syndrome Flashcards
what is testicular dysgenesis syndrome?
Hypothetical disease that groups 4 separate conditions leading to male infertility on the basis of a common origin
what are the 4 conditions that make up testicular dysgenesis syndrome?
Testicular cancer
Lowered sperm count
Cryptorchidism
Hypospadia
what is a potential cause of testicular dysgenesis syndrome?
endocrine-disrupting chemicals in the environment
what are some endocrine-disrupting chemicals in the environment?
Contraceptive pill metabolites,
Plasticisers (e.g. phthalates, bisphenol A),
Dietary phytoestrogens, especially from soy products. Naturally occurring compounds with very weak oestrogen-like activity (Genistein, daidzein, etc).
how could endocrine disruptors lead to testicular dysgenesis syndrome?
Could interfere with developmental processes such as FSH regulation of Sertoli cell proliferation or proliferation of germ cells, causing permanent effects in the adult.
how can endocrine disruptors impact Sertoli cells?
FSH stimulates Sertoli cell proliferation, so endocrine disruptors might reduce Sertoli cell numbers in adult.
what is important about the number of Sertoli cells and germ cells?
Each S. cell can only support a fixed number of germ cells, so this would reduce adult sperm count.
how can endocrine-disruptors impair cell proliferation?
Endocrine-disruptors could impair embryonic/foetal germ cell proliferation, eg causing gonocytes to cease dividing & transform into Carcinoma In Situ (CIS) cells.
what damage can be done to Leydig cells?
Could also cause long-term damage to Leydig cells leading to impaired function in later life – compensated Leydig cell dysfunction
what is the evidence of the effects of endocrine-disruptors?
Good evidence of effects in aquatic species:
- fish with reproductive system defects found near sewage outlets;
- alligators etc with reduced penis length & skewed sex ratios in aquatic reptiles in contaminated lakes (e.g. Lake Apopka).
- Can be shown experimentally in laboratory mammals. E.g. dibutylhexylphthalate (DBHP), bisphenol A: cause wide range of such defects in rodent species when administered at appropriate time during embryonic/foetal development.
what does 1992 Carlsen et al claim?
50 % reduction in human sperm counts in previous 50 years using a meta-analysis of published papers that presented a ‘normal’ sperm count§
is Carlsen et al study approved?
no the original study is deeply flawed
what does the epidemiological data from cancer registries confirm?
the incidence of testicular cancer is rising everywhere.
what has been established about the origins of testicular cancer?
that it is an interruption of gonocyte development that converts them into CIS cells. These sit dormant until after puberty, then may reactivate to cause cancer
why has TDS been proposed as a syndrome?
because endocrine disruption can be hypothesised to be responsible for all 4 of the conditions involved.
